It has long been customary in classifying diseases of the nervous system to group them as degenerative, thereby indicating they are characterized by a gradually evolving, relentlessly progressive, neuronal death. Science has shown that a considerable portion of disorders that are classed as degenerative are associated with genetic predisposition which results in a pattern of dominant or recessive inheritance. However, others, although they do not differ in a fundamental way from the hereditary disorders, may occur only sporadically as isolated instances within a given family.
As a consequence, since by definition, classification of degenerative diseases cannot be based upon exact knowledge of their cause or pathogenesis, subdivision of these diseases into individual syndromes rests upon descriptive criteria based largely upon pathologic anatomy and consideration of clinical aspects. As a result, this group of diseases presents itself in the form of several clinical syndromes. However, apart from the general differences that allows the distinction of one syndrome from another, there are certain general attributes which typify this entire class of disorders.
The degenerative diseases of the nervous system can typically be divided into disorders characterized by progressive dementia in the absence of other prominent neurologic signs.
In recent years, it has become evident that perturbation of nicotinic cholinergic neurotransmission can result in a number of neurodegenerative, neuropsychiatric and neurological disorders. Indications that may be serviced via therapy using nicotinic acetylcholine receptor (nAChR) ligands include Alzheimer's disease, Parkinson's disease, Tourette's syndrome, depression, attention deficit disorder (ADHD), schizophrenia, Lewy body dementia, acute and chronic pain, anxiety disorders, ulcerative colitis, and autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).
Nicotine has a wide variety of pharmacological effects. A number of compounds that affect the nAChRs are known to have utility for treating a wide variety of conditions and disorders.
While many neurological disorders are peripherally manifested, (e.g., ulcerative colitis), a large fraction of neurological disorders can be considered CNS disorders. A number of CNS disorders can be attributed to the disfunction of neurotransmitter systems such as dopamine, choline, norepinephrine, serotonin, etc. CNS disorders which may be classified as such include mild cognitive impairment, age-related cognitive decline, vascular dementia, presenile dementia (early-onset Alzheimer's disease), Alzheimer's disease, Parkinson's disease dementia, attention-deficit hyperactivity disorder, anxiety, dyslexia, schizophrenia, tardive dyskinesia, Tourette's syndrome, depression, and addiction.
Administration of an agonist or partial agonist of nAChRs to a patient suffering certain neurological disorders would provide a useful method for the treatment and/or prevention of those neurological disorders (e.g., CNS disorders). It would be desirable to provide patients suffering from CNS disorders related to deficiency of cholinergic transmission with a pharmaceutical composition which has nicotinic pharmacology and which has a beneficial effect on the disorder without significant adverse side effects. It is expected that a pharmaceutical composition incorporating a compound which interacts with neuronal nicotinic receptors as an agonist or partial agonist, when applied at amounts sufficient to affect functioning of the CNS, will not affect significantly those nicotinic receptor subtypes which have the potential to induce undesirable effects, for example, at skeletal muscle and ganglionic sites.